Army screens drugs for SARS treatment
Thursday, April 10, 2003
Scientists hoping a cure is already on the shelf will test at least 2,000 drugs against the frightening SARS virus, although some doubt anything they find will stop the flu-like disease once it gets a foothold.
This search is intended to find an immediate therapy for severe acute respiratory syndrome, or one that could be developed quickly. There is now no proven cure, only treatment that relieves symptoms.
Scientists are almost positive SARS is caused by a newly discovered member of the coronavirus family. Until now, these bugs have been known only to trigger colds or mild diarrhea, so no one has ever tried very hard to find a treatment.
The National Institute of Allergy and Infectious Diseases is gathering up the 30 or so antiviral drugs on the market, about 800 drugs approved for other uses, plus more than 1,000 that are still being developed.
They are being tested at the U.S. Army Medical Research Institute for Infectious Diseases at Fort Detrick, Md.
The lab can test 150 to 200 a drugs week and has started with the most obvious antiviral medicines.
But so far, "nothing looks very promising, to be honest," Army research scientist Peter Jahrling said Wednesday.
At the same time, another team at the University of Virginia hopes soon to enroll SARS victims to test a two-drug strategy already used by some doctors in Hong Kong and Canada, although many are skeptical it will work.
Furthermore, experts expect much more study of the virus. Scientists will be looking for weaknesses in the bug that might be exploited, as well as a better understanding of how the immune system responds to it. Some experts believe the body's own defenses are part of the problem.
Deciphering the virus' innermost workings might in the end lead to the most effective drugs. But designing a medicine from scratch is a slow and daunting process, requiring years of testing.
"It's a fact of life we can't get around that from the design of a drug on a computer to the point where it can be given to people takes at the very best five years. We hope something will come along in this process that will prove to be effective," said Dr. Catherine Laughlin, virology chief at the infectious disease institute.
About 50 drug companies took part in a recent conference call with the institute and the Centers for Disease Control and Prevention, and several said they had compounds in development that they would like try against SARS.
"This clearly isn't a market for anybody, but people feel if they have drugs on hand that can help, they want to make them available," Laughlin said.
Even if a drug knocks out the virus, it still might not cure SARS. In some infections, much of the damage results from the overwhelming chemical counterattack by the immune system. This cytokine storm, as its called, is intended to kill the virus. But it can have unintended consequences, such as inflammation, leaky blood vessels and even pneumonia, a hallmark of SARS.
"The infection comes on so quickly and you get so sick so fast that it's unlikely that an antiviral will be rapidly effective," said Dr. John Zaia, virology chairman at City of Hope National Medical Center in Duarte, Calif. "It may be that the virus has started a process that cannot be stopped."
Still, experiments in animals, which have their own versions of the coronavirus, suggest that stopping the virus may help, even when the disease is in full force.
"It all depends on what the virus is doing," damaging the lungs directly or triggering an immune system backlash, said Dr. Mark Denison, a coronavirus researcher at Vanderbilt University. "If it's the virus causing tremendous damage by its growth, and you interfere at midpoint, you might make quite a dramatic difference for the person."
Dr. Frederick Hayden of the University of Virginia hopes to lead a test of the drug ribavirin, an antiviral medicine, and steroids, which tamp down the immune system. Ribavirin is used to treat respiratory syncytial virus, a major cause of pneumonia in infants.
Doctors in Hong Kong and Canada say the combination may help, although there is no experimental proof of that. In Hayden's federally financed study, people with moderate SARS will be given either ribavirin or dummy medicine, and those seriously ill will be randomly given a steroid, as well.
While agreeing the strategy needs to be tested, several experts hold out little hope it will make much difference. "Many clinicians have tried ribavirin," said CDC head Dr. Julie Gerberding. "I don't think it looks real promising for that to be a solution."
Among the drugs being tested at the Army lab are a wide range of compounds intended to stop viruses from making new copies of themselves. Although virtually all of these drugs were tailored for other viruses, the researchers said there is a chance they might work on coronavirus, too.
If a coronavirus drug must be designed from the ground up, scientists say the virus offers several possible targets in its life cycle. Similar strategies have led to treatments for AIDS and herpes, among other viral diseases.
At least one company says it may be able to produce a new drug fast. AVI BioPharma in Portland, Ore. uses a technique that disables viral genes and has already made experimental drugs for coronaviruses that cause illnesses in cats and lab mice.
Using the same technology, officials say they should be able to make a drug that would attack the SARS virus within a week of receiving its genetic code, which the CDC hopes to finish reading soon.
EDITOR'S NOTE: Medical Editor Daniel Q. Haney is a special correspondent for The Associated Press.
On the Net